Prostate cancer is the most common malignancy and the second leading cause of death among men in the U.S. (Li et al., Biochim. Biophys. Acta, 1704: 87-102 (2004)). The National Cancer Institute (NCI) estimates that in 2013, over 230,000 new cases of prostate cancer will be diagnosed, and over 29,000 men will die of prostate cancer in the United States. The prostate-specific antigen or PSA test continues to be widely used in the early detection of prostate cancer. While the PSA test has resulted in the majority of prostate cancer cases being diagnosed in asymptomatic men (Mettlin et al., Cancer, 83(8): 1679-1684 (1998a); Mettlin et al., Cancer, 82(2): 249-251 (1998b); Humphrey et al., J. Urol., 155: 816-820 (1996); and Grossfeld et al., Epidemiol. Rev., 23(1): 173-180 (2001)), the PSA test suffers from poor specificity, which can be as low as 33% when a PSA cut-off level of 2.6 ng/mL is used (Thompson et al., N. Engl. J. Med., 350: 2239-2246 (2004)), even though the sensitivity can be as high as 83%. The poor specificity of the PSA test is a direct result of increased secretion of PSA in other diseases of the prostate, such as benign prostate hyperplasia (BPH) and prostatitis. Thus, an elevated PSA level indicates the need for additional screening typically in the form of needle biopsy. Ultimately, the results of needle biopsies lead to the diagnoses of prostate cancer. Over 1 million needle biopsies of prostates are performed each year at a cost of about $1,500 each and much discomfort to the patient. However, less than 200,000 of these result in a diagnosis of prostate cancer. Therefore, the majority of needle biopsies are being performed needlessly.
Currently, several diagnostic markers are used clinically to distinguish benign prostate tissue from malignant prostate tissue, including, for example, alpha-methylacyl-CoA racemase (AMACR, p504s) (Zhou et al., Amer. J. Surgical Pathology, 27(6): 772-778 (2003)) and the TMPRSS2-ERG fusion gene (Yu et al., Cancer Cell, 17(5): 443-54 (2010)). These markers, however, lack the specificity needed for consistently reliable diagnoses. Similarly, prognostic biomarkers such as the TMPRSS2-ERG gene fusion, PTEN deletion, and SPINK1 overexpression also lack the specificity to assess a wide range of prostate cancers, leaving a significant number of prostate cancers without further prognostic information apart from calculating a cancer's Gleason score. Currently there are no known biomarkers that can indicate prostate cancers that have invaded into the periprostatic soft tissue.
Thus, there is a need for non-invasive methods of diagnosing and prognosticating prostate cancer, as well as improved methods for treating prostate cancer. The invention provides such methods.